Spinal circuits for sensorimotor integration and interlimb coordination during locomotion

运动过程中用于感觉运动整合和肢体间协调的脊髓回路

• 批准号: 10267168
• 负责人: Simon Michael Danner
• 金额: $ 33.73万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-21 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10267168
• 关键词: Address; Anatomy; Animals; Behavioral; Brain Stem; Clinical Research; Collaborations; Comb animal structure; Computer Models; Contralateral; Cutaneous; Degenerative Disorder; Elderly; Electrophysiology (science); Equilibrium; Excision; Experimental Models; Feedback; Fiber; Foundations; Future; Gait; Gene Delivery; Hindlimb; Impairment; Individual; Interneurons; Ipsilateral; Knowledge; Limb structure; Literature; Local Anesthetics; Locomotion; Methods; Modeling; Motor Activity; Motor Neurons; Mus; Muscle; Musculoskeletal; Musculoskeletal System; Mutant Strains Mice; Neural Network Simulation; Neurons; Pathway interactions; Pattern; Pattern Formation; Peripheral Nerves; Phase; Phase Transition; Population; Process; Public Health; Recovery; Reflex action; Research Personnel; Rest; Role; Sensory; Signal Transduction; Speed; Spinal; Spinal Cord; Spinal cord injury; Surface; Syndrome; System; Testing; Virus; Wild Type Mouse; Work; base; biomechanical model; connectome; design; experimental study; improved; in vivo; insight; interdisciplinary approach; kinematics; locomotor control; motor disorder; mouse genetics; mouse model; multidisciplinary; neural circuit; neural model; neuromechanism; neuroregulation; novel; predictive modeling; rehabilitation strategy; relating to nervous system; response; somatosensory; tool

Somatosensory feedback from the limbs is essential for locomotion and its recovery after spinal cord injury. To achieve stable locomotion, the spinal cord needs to process afferent feedback signals and properly adjust muscle activation and interlimb coordination. Crossed-reflex pathways, specifically, are important for gait stability and balance, which are impaired in various motor disorders and in the elderly. Recently, significant progress has been made in decoding the organization and function of the central spinal locomotor circuitry and its brainstem command system. But the interactions of somatosensory feedback with the spinal circuitry during locomotion have yet to be understood on the same level of detail. In this project we propose to address this gap of knowledge by combing mouse genetics, in vivo electrophysiology, and behavioral analyses with computational modeling of spinal circuits and the musculoskeletal system to systematically dissect sensory afferent connectivity to the locomotor circuitry, including genetically identified neuron populations, and their function in interlimb coordination. Studying the organization of crossed reflexes and their interactions with spinal locomotor circuitry will provide critical information for rehabilitative strategies. This multidisciplinary project will be performed in close interactive collaboration between two investigators with strong and complementary expertise in computational (Simon Danner, PI) and experimental studies of neural control of locomotion (Turgay Akay, Co-PI). The project has the following three aims: (1) Delineate the involvement of multiple spinal interneurons in the processing of sensory information and interlimb coordination by studying crossed reflexes at rest and during locomotion; (2) Design a predictive computational model of the spinal locomotor circuitry and its interactions with the mouse musculoskeletal system; (3) Integrate modeling and experimentation to uncover underlying neural mechanisms. The model will be used to derive informative predictions that will then be tested experimentally. This process has the advantage of providing an explicit and consistent theoretical framework for experimentation, thereby reducing the number of necessary experiments while increasing the information gained per experiment. In summary, the proposed multidisciplinary approach is based on state-of-art experimental and modeling methods and will provide important and novel insights into the neural organization of the spinal locomotor circuitry responsible for sensorimotor integration and interlimb coordination during locomotion that cannot be obtained by experimentation or modeling alone.

来自四肢的体感反馈对于脊髓损伤后的运动及其恢复至关重要。达到 稳定的运动，脊髓需要处理传入的反馈信号并适当地调整肌肉的激活和 四肢间的协调。具体来说，交叉反射通路对于步态稳定性和平衡非常重要， 各种运动障碍和老年人受损。最近，在解码方面取得了重大进展。 中枢脊髓运动回路及其脑干指挥系统的组织和功能。但互动 运动过程中脊髓回路的体感反馈的机制尚未在相同的细节水平上得到理解。 在这个项目中，我们建议通过结合小鼠遗传学、体内电生理学和 通过脊髓回路和肌肉骨骼系统的计算模型进行行为分析，以系统地剖析 感觉传入连接到运动回路，包括基因识别的神经元群及其 肢体间协调功能。研究交叉反射的组织及其与脊髓运动的相互作用 电路将为康复策略提供关键信息。这个多学科项目将在 两位在计算方面拥有强大且互补的专业知识的研究人员之间密切互动合作（西蒙 Danner，PI）和运动神经控制的实验研究（Turgay Akay，Co-PI）。该项目有以下内容 三个目标：（1）描述多个脊髓中间神经元参与感觉信息的处理和 通过研究休息和运动过程中的交叉反射来进行肢体间协调； (2) 设计预测计算 脊髓运动回路模型及其与小鼠肌肉骨骼系统的相互作用； (3) 集成建模 和实验来揭示潜在的神经机制。该模型将用于得出信息丰富的预测 然后将进行实验测试。该过程的优点是提供了明确且一致的理论 实验框架，从而减少必要实验的数量，同时增加信息 每次实验获得的。总之，所提出的多学科方法基于最先进的实验和 建模方法将为脊髓运动的神经组织提供重要而新颖的见解 负责运动过程中感觉运动整合和肢体间协调的电路，这是无法通过 单独进行实验或建模。